Summary/Abstract The genetic basis of human disease has been an underlying focus the biomedical sciences for almost a century, and was a major motivating factor behind the human genome project. With the explosion of genomic data that has brought on the age of personalized medicine, the role of computational analyses has become critical for all forms of inquiry. Increasingly, clinicians and basic scientists are confronted with massive genomic data sets that contain important answers to medical problems, but discovery is hindered by limited computational expertise. The COBRE Center for Computational Biology of Human Disease is intended to embrace this age of genomic medicine from an explicitly computational angle. Five Junior Investigators will lead research projects on that focus on different diseases such as cancer, respiratory and age- related diseases and preeclampsia, but are united by common computational and bioinformatic challenges of large genomic data sets. By building a collaborative Center of empirical and computational scientists, we will be able to advance new discoveries, algorithms and genetic and genomic screening approaches with direct relevance to several human diseases. The associated Administrative Core of this Center will provide a strong supportive context for these specific research projects, while also providing a broad base of support for the growth of collaborative research efforts on human disease at Brown University and its Affiliated Hospitals.